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Endocytosis and transcytosis of gliadin peptides.

ABSTRACT: BACKGROUND:Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Some gliadin peptides are not digested by intestinal proteases and can have different biological effects. Gliadin peptides can induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptides 31-43 and 31-55) is the cytokine interleukin-15 (IL-15). Other peptides such as the 33 mer containing the P57-68 sequence, after tissue transglutaminase deamidation, are well presented to T cell in the intestine and can induce an adaptive immune response. FINDINGS:In this paper, we review the recent studies on the digestion of gliadin and the peptides released by the digestion process. We will also discuss the mechanisms responsible for the internalization and transcytosis of indigested gliadin peptides in the intestinal epithelium. CONCLUSIONS:Gliadin is not completely digested by the intestinal proteases producing bioactive peptides that have different biological effects. These peptides are internalized in the cells by an active process of endocytosis and can traverse the intestinal mucosa with different kinetics and immunological effects. In vivo findings will also be discussed.

SUBMITTER: Barone MV

PROVIDER: S-EPMC4755952 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Endocytosis and transcytosis of gliadin peptides.

Barone M Vittoria MV Zimmer K Peter KP

Molecular and cellular pediatrics 20160216 1

<h4>Background</h4>Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Some gliadin peptides are not digested by intestinal proteases and can have different biological effects. Gliadin peptides can induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptides 31-43 and 31-55) is the cytokine interleukin-15 (IL-15). Other pepti ...[more]

PMID: 26883352

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Project description:Coeliac disease (CD) is a common and complex disorder of the small intestine caused by intolerance to wheat gluten and related edible cereals like barley and rye. Peptides originating from incomplete gliadin digestion activate the lamina propria infiltrating T cells to release proinflammatory cytokines, which in turn cause profound tissue remodelling of the small intestinal wall. There is no cure for CD except refraining from consuming gluten-containing products.Phage from a random oligomer display library were enriched by repeated pannings against immobilised gliadin proteins. Phage from the final panning round were plated, individual plaques picked, incubated with host bacteria, amplified to a population size of 1011 to 1012 and purified. DNA was isolated from 1000 purified phage populations and the region covering the 36 bp oligonucleotide insert from which the displayed peptides were translated, was sequenced. Altogether more than 150 different peptide-encoding sequences were identified, many of which were repeatedly isolated under various experimental conditions. Amplified phage populations, each expressing a single peptide, were tested first in pools and then one by one for their ability to inhibit binding of human anti-gliadin antibodies in ELISA assays. These experiments showed that several of the different peptide-expressing phage tested inhibited the interaction between gliadin and anti-gliadin antibodies. Finally, four different peptide-encoding sequences were selected for further analysis, and the corresponding 12-mer peptides were synthesised in vitro. By ELISA assays it was demonstrated that several of the peptides inhibited the interaction between gliadin molecules and serum anti-gliadin antibodies. Moreover, ELISA competition experiments as well as dot-blot and western blot revealed that the different peptides interacted with different molecular sites of gliadin.We believe that several of the isolated and characterised gliadin-binding peptides described here could provide valuable tools for researchers in the field of CD by facilitating studies on localisation and uptake of various gliadin peptides in the small intestine. In future work, the potential of these peptides to detoxify gluten will be investigated.

Dataset Information

Endocytosis and transcytosis of gliadin peptides.

Publications

Endocytosis and transcytosis of gliadin peptides.

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